High-fat diet (HFD), an unfortunate lifestyle choice common in the Western world, is associated with inflammation and thereby is regarded as a risk factor for various diseases including obesity, diabetes, and cancer. The molecular mechanism(s) responsible for HFD-induced inflammation in the prostate gland are not well understood. Estrogen receptor alpha (ER-α), signal transducer and activator of transcription (Stat)-3 and aromatase are important signaling molecules constitutively activated during inflammation and have been shown to be upregulated in prostate cancer. We have previously reported that HFD activates a pro-inflammatory response in the prostate through elevated expression of Stat-3 (Prostate 72:233-43, 2012). In the current study, we sought to investigate a possible link between intraprostatic inflammation, HFD feeding, signaling molecules involved in inflammation viz. ER-α, Stat-3, p-Stat3 (Ser727) and aromatase. C57BL/6 mice were fed either a regular diet (RD) or a HFD for 4, 8 and 12 weeks. Serum, visceral fat and prostate tissues were obtained for analysis. HFD intake caused an increase in fat and serum testosterone levels. No significant changes were observed in the testosterone levels in the prostate. A marked increase in estrogen levels was noted in the prostate and visceral fat at 8 weeks of HFD intake. HFD feeding resulted in a significant increase in the expression of aromatase, ER-α, Stat-3 and p-Stat3 (Ser727) at the message and protein levels. Immunoprecipitation and ChIP analysis demonstrated an increased association between aromatase, p-Stat-3 and ER-α in the HFD group. IHC analysis revealed higher expression of Stat-3, ER-α and aromatase in the prostate, accompanied by the morphologic evidence of increased intraprostatic inflammation in the HFD group. Taken together, our findings suggest that HFD increases estrogen levels by increased binding of ER-α and p-Stat-3 to the promoter of aromatase and their interaction is associated with increased intraprostatic inflammation which might contribute to the initiation and development of prostate cancer.

Citation Format: Natarajan Bhaskaran, Sanjeev Shukla, Vijay S. Thakur, Melissa A. Babcook, Gregory T. MacLennan, Guiming Liu, Firouz Daneshgari, Sanjay Gupta. High-fat diet induces inflammation by increasing estrogen levels through Stat3, estrogen receptor alpha and aromatase in the mouse prostate. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 5452. doi:10.1158/1538-7445.AM2013-5452

©2013 American Association for Cancer Research
2013